Liver-directed gene therapy: promises, problems and prospects at the turn of the century

Although liver-directed gene therapy arrived later than gene therapy direct ed at bone marrow cells, intrinsic advantages of the liver as a target orga n make it likely that gene therapy for liver diseases will be among the fir st therapeutically relevant applications of this treatment modality at the onset of the 21st century, Vectorology for gene transfer to the river is ad vancing rapidly, and it is safe to predict that gene therapy vehicles that will be in clinical use a decade from now have not yet been developed. None of the currently available modes of gene transfer to the liver is optimal for all types of applications. Nonetheless, the concerted effort of many in vestigators has provided a wide choice of non-viral and viral vectors for g ene transfer to the liver for use in specific situations. Original strategi es for liver-directed gene therapy included substitution of missing gene pr oducts, overexpression of intrinsic or extrinsic genes and inhibition of ex pression of specific genes. To the list is now added the possibility of sit e-specific correction or generation of mutations within specific gems in so matic cells of living adult animals Thus, despite some initial faux pas, li ver-directed gene therapy is poised to make an important impact on health c are in the year 2000 and beyond.